{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:43:42Z","timestamp":1792471422970,"version":"4.5.0"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Aggressive variants of prostate cancer pose significant diagnostic and prognostic challenges due to atypical imaging appearances, variable prostate-specific antigen behavior, and distinct molecular features. Conventional imaging may underestimate their biological aggressiveness. This review aimed to synthesize current evidence on imaging characteristics, biomarker dynamics, tumor localization, histology, and radiomic features of aggressive prostate cancer variants, and to evaluate the potential role of radiomics in early recognition and risk stratification. Methods: A structured narrative review was performed of studies reporting imaging, clinical, and molecular features of aggressive prostate cancer variants. Imaging modalities included multiparametric magnetic resonance imaging, positron emission tomography with prostate-specific membrane antigen or fluorodeoxyglucose, bone scintigraphy, and transrectal ultrasound. Data on prostate-specific antigen levels and kinetics, intraprostatic tumor location, tumor size, metastatic patterns, and molecular alterations were extracted. Evidence for rare entities such as basaloid and primary squamous carcinomas was derived from published case reports and series, while selected variants were complemented by institutional imaging and histopathologic observations. Results: Neuroendocrine and small cell carcinomas frequently showed low prostate-specific antigen levels, high fluorodeoxyglucose uptake, low prostate-specific membrane antigen expression, and central or transitional zone involvement with large tumor size at diagnosis. Ductal adenocarcinoma demonstrated marked diffusion restriction and elevated prostate-specific antigen, whereas basal cell carcinoma often appeared inconspicuous on conventional imaging. Radiomic analysis consistently captured tumor heterogeneity and spatial complexity beyond standard qualitative metrics. Conclusions: Aggressive prostate cancer variants represent a diagnostic blind spot in routine imaging. Radiomics offers complementary quantitative information that may improve early detection, subtype differentiation, and risk stratification when integrated into multimodal imaging workflows. Further prospective and radiogenomic studies are warranted to validate these findings.<\/jats:p>","DOI":"10.3390\/cancers18050780","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:18:45Z","timestamp":1772554725000},"page":"780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Radiomics-Based Characterization of Aggressive Prostate Cancer Variants: Diagnostic Challenges and Opportunities"],"prefix":"10.3390","volume":"18","author":[{"given":"Katarzyna","family":"Sklinda","sequence":"first","affiliation":[{"name":"Centre of Radiological Diagnostics, National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5553-3680","authenticated-orcid":false,"given":"Martyna","family":"Rajca","sequence":"additional","affiliation":[{"name":"Centre of Radiological Diagnostics, National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Kasprowicz","sequence":"additional","affiliation":[{"name":"Clinical Department of Urology and Oncological Urology, National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3429-4337","authenticated-orcid":false,"given":"\u0141ukasz","family":"Micha\u0142owski","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Warsaw, Pawi\u0144skiego, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Ma\u0142ek","sequence":"additional","affiliation":[{"name":"Clinical Department of Urology and Oncological Urology, National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6505-5369","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Olczak","sequence":"additional","affiliation":[{"name":"Clinical Department of Urology and Oncological Urology, National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Walecki","sequence":"additional","affiliation":[{"name":"Centre of Radiological Diagnostics, National Medical Institute of the Ministry of the Interior and Administration, Wo\u0142oska 137, 02-507 Warsaw, Poland"},{"name":"Department of Radiology, Centre of Postgraduate Medical Education, Marymoncka 99\/103, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/PAS.0000000000000530","article-title":"The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System","volume":"40","author":"Epstein","year":"2016","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e386","DOI":"10.1200\/JCO.2011.41.5166","article-title":"Challenges in Recognizing Treatment-Related Neuroendocrine Prostate Cancer","volume":"30","author":"Beltran","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1200\/JCO.2013.54.3553","article-title":"Neuroendocrine Prostate Cancer (NEPC) Progressing from Conventional Prostatic Adenocarcinoma: Factors Associated with Time to Development of NEPC and Survival from NEPC Diagnosis\u2014A Systematic Review and Pooled Analysis","volume":"32","author":"Wang","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1200\/JCO.2017.77.6880","article-title":"Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study","volume":"36","author":"Aggarwal","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nm.4045","article-title":"Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer","volume":"22","author":"Beltran","year":"2016","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1038\/s41379-021-00860-4","article-title":"Comedonecrosis Gleason pattern 5 is associated with worse clinical outcome in operated prostate cancer patients","volume":"34","author":"Hansum","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dorado, C.Q., Ram\u00edrez, A.S., P\u00e9rez, M.P., Centeno, M.S., Mici, L.P., G\u00fcemez, C.M., Acosta, E.A., Luis, G.C., Costal, M., and Diez, P.T. (2025). Redefining Prostate Cancer Precision: Radiogenomics, Theragnostics, and AI-Driven Biomarkers. Cancers, 17.","DOI":"10.20944\/preprints202511.0248.v1"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Urso, L., Badrane, I., Manco, L., Castello, A., Lancia, F., Collavino, J., Crestani, A., Castellani, M., Cittanti, C., and Bartolomei, M. (2025). The Role of Radiomics and Artificial Intelligence Applied to Staging PSMA PET in Assessing Prostate Cancer Aggressiveness. J. Clin. Med., 14.","DOI":"10.3390\/jcm14103318"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1007\/s00330-023-10427-3","article-title":"Radiomics for the identification of extraprostatic extension with prostate MRI: A systematic review and meta-analysis","volume":"34","author":"Ponsiglione","year":"2024","journal-title":"Eur. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1016\/j.acra.2024.12.006","article-title":"MRI-based Radiomics for Predicting Prostate Cancer Grade Groups: A Systematic Review and Meta-analysis","volume":"32","author":"Lomer","year":"2025","journal-title":"Acad. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhang, C., Chen, B., and Wu, Q. (2023). Basal cell carcinoma of the prostate with squamous metaplasia: A case report and literature review. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1094943"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.humpath.2015.02.004","article-title":"Basal cell carcinoma of the prostate is an aggressive tumor with frequent loss of PTEN expression and overexpression of EGFR","volume":"46","author":"Simper","year":"2015","journal-title":"Hum. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/iju5.12143","article-title":"Primary basal cell carcinoma of the prostate with concurrent adenocarcinoma","volume":"3","author":"Hennes","year":"2020","journal-title":"IJU Case Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dong, S., Liu, Q., Xu, Z., and Wang, H. (2020). An Unusual Case of Metastatic Basal Cell Carcinoma of the Prostate: A Case Report and Literature Review. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00859"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12301-021-00178-2","article-title":"Prostatic basal cell carcinoma treated by chemoradiation with weekly cisplatine: Case report and literature review","volume":"27","author":"Ridai","year":"2021","journal-title":"Afr. J. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ajpath.2022.09.010","article-title":"Genomic Characterization of Prostatic Basal Cell Carcinoma","volume":"193","author":"Low","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref_18","first-page":"187","article-title":"Basal Cell Carcinoma of the Prostate Misdiagnosed as High-Grade Urothelial Cancer\u2014A Case Report of a Diagnostic Pitfall","volume":"15","author":"Taskovska","year":"2023","journal-title":"Res. Rep. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101427","DOI":"10.1016\/j.adro.2023.101427","article-title":"On Complete Clinical Response of Basal Cell Carcinoma of the Prostate After Definitive Concurrent Chemoradiation","volume":"9","author":"Toesca","year":"2024","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_20","first-page":"101478","article-title":"Primary prostatic squamous cell carcinoma","volume":"34","author":"Hanna","year":"2021","journal-title":"Urol. Case Rep."},{"key":"ref_21","first-page":"101796","article-title":"Squamous cell carcinoma of the prostate with lower urinary tract symptoms: A case report","volume":"39","author":"He","year":"2021","journal-title":"Urol. Case Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/iju5.12365","article-title":"Successful treatment with DCF chemotherapy and radiotherapy for primary squamous cell carcinoma of the prostate","volume":"4","author":"Atagi","year":"2021","journal-title":"IJU Case Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/iju5.12466","article-title":"Squamous cell carcinoma of the prostate with SMARCA4 alteration in a Japanese patient","volume":"5","author":"Kaneko","year":"2022","journal-title":"IJU Case Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"FSO18","DOI":"10.4155\/fso.15.16","article-title":"Primary Squamous Cell Carcinoma of the Prostate: A Case Report of a Rare Clinical Entity","volume":"1","author":"Biswas","year":"2015","journal-title":"Future Sci. OA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.eururo.2022.07.032","article-title":"Tumors of the Urinary System and Male Genital Organs: 2022 World Health Organization Classification and Multidisciplinarity","volume":"82","author":"Montironi","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1158\/2159-8290.CD-11-0130","article-title":"Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets","volume":"1","author":"Beltran","year":"2011","journal-title":"Cancer Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1365-2559.2011.04039.x","article-title":"Histological variants of prostatic carcinoma and their significance","volume":"60","author":"Humphrey","year":"2011","journal-title":"Histopathology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/j.1464-410X.2011.10520.x","article-title":"Incidence and outcomes of ductal carcinoma of the prostate in the USA: Analysis of data from the Surveillance, Epidemiology, and End Results program","volume":"109","author":"Meeks","year":"2012","journal-title":"BJU Int."},{"key":"ref_29","first-page":"379","article-title":"Squamous cell carcinoma of the prostate with concomitant hypercalcemia and normal serum prostate-specific antigen levels","volume":"131","author":"Hulak","year":"2021","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6916","DOI":"10.1158\/1078-0432.CCR-19-1423","article-title":"The Role of Lineage Plasticity in Prostate Cancer Therapy Resistance","volume":"25","author":"Beltran","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.eururo.2015.08.052","article-title":"PI-RADS Prostate Imaging\u2014Reporting and Data System: 2015, Version 2","volume":"69","author":"Weinreb","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"432","DOI":"10.21037\/tcr.2016.06.20","article-title":"Prostate cancer radiomics and the promise of radiogenomics","volume":"5","author":"Stoyanova","year":"2016","journal-title":"Transl. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1148\/radiol.2015151169","article-title":"Radiomics: Images Are More than Pictures, They Are Data","volume":"278","author":"Gillies","year":"2016","journal-title":"Radiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jmri.25335","article-title":"Haralick textural features on T2-weighted MRI are associated with biochemical recurrence following radiotherapy for peripheral zone prostate cancer","volume":"45","author":"Gnep","year":"2017","journal-title":"J. Magn. Reson. Imaging."},{"key":"ref_35","unstructured":"Epstein, J.I., and Netto, G.J. (2014). Biopsy Interpretation of the Prostate, Wolters Kluwer Health. [5th ed.]."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1097\/RLU.0000000000004230","article-title":"68Ga-PSMA-11 and 18F-FDG PET\/CT in a case of ductal adenocarcinoma of the prostate","volume":"47","author":"Qiu","year":"2022","journal-title":"Clin. Nucl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1097\/RLU.0000000000000280","article-title":"MRI, enhanced CT, and FDG PET\/CT in basal cell carcinoma of the prostate","volume":"39","author":"Dong","year":"2014","journal-title":"Clin. Nucl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.7150\/thno.32376","article-title":"Radiomic features from PSMA PET for non-invasive intraprostatic tumor discrimination and characterization in patients with intermediate- and high-risk prostate cancer\u2014A comparison study with histology reference","volume":"9","author":"Zamboglou","year":"2019","journal-title":"Theranostics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"888","DOI":"10.2967\/jnumed.123.267260","article-title":"A systematic review on the diagnostic value of fibroblast activation protein inhibitor PET\/CT in genitourinary cancers","volume":"65","author":"Hagens","year":"2024","journal-title":"J. Nucl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s12149-025-02022-x","article-title":"FAPI radiopharmaceuticals in nuclear oncology and theranostics of solid tumours: Are we nearer to surrounding the hallmarks of cancer?","volume":"39","author":"Almeida","year":"2025","journal-title":"Ann. Nucl. Med."},{"key":"ref_41","first-page":"410","article-title":"Small cell prostate cancer: Center review of two cases and testimony of a rare and aggressive disease","volume":"13","author":"Salihu","year":"2024","journal-title":"Case Rep. Clin. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00345-011-0747-3","article-title":"Novel contrast-enhanced ultrasound imaging in prostate cancer","volume":"29","author":"Smeenge","year":"2011","journal-title":"World J. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"302","DOI":"10.5489\/cuaj.2976","article-title":"Prostatic ductal adenocarcinoma: An aggressive variant that is underdiagnosed and undersampled on transrectal ultrasound (TRUS)-guided needle biopsy","volume":"9","author":"Gulavita","year":"2015","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13S","DOI":"10.2967\/jnumed.116.177196","article-title":"Utility of Ultrasound in the Diagnosis, Treatment, and Follow-up of Prostate Cancer: State of the Art","volume":"57","author":"Chen","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4103\/0970-1591.203414","article-title":"Multiparametric magnetic resonance imaging-transrectal ultrasound fusion prostate biopsy: A prospective, single-centre study","volume":"33","author":"Gupta","year":"2017","journal-title":"Indian J. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e230138","DOI":"10.1148\/ryai.230138","article-title":"Deep Learning Prosta MRI Segmentation Accuracy and Robustness: A Systematic Review","volume":"6","author":"Fassia","year":"2024","journal-title":"Radiol. Artif. Intell."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1148\/radiol.2020191145","article-title":"The Image Biomarker Standardization Initiative: Standardized Quantitative Radiomics for High-Throughput Image-based Phenotyping","volume":"295","author":"Zwanenburg","year":"2020","journal-title":"Radiology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13244-023-01415-8","article-title":"CheckList for EvaluAtion of Radiomics research (CLEAR): A step-by-step reporting guideline for authors and reviewers endorsed by ESR and EuSoMII","volume":"14","author":"Kocak","year":"2023","journal-title":"Insights Into Imaging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e078378","DOI":"10.1136\/bmj-2023-078378","article-title":"TRIPOD+AI statement: Updated guidance for reporting clinical prediction models that use regression or machine learning methods","volume":"385","author":"Collins","year":"2024","journal-title":"BMJ"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1053\/j.seminoncol.2006.10.026","article-title":"Unusual and underappreciated: Small cell carcinoma of the prostate","volume":"34","author":"Palmgren","year":"2007","journal-title":"Semin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00330-019-06360-z","article-title":"Quality of science and reporting of radiomics in oncologic studies: Room for improvement according to radiomics quality score and TRIPOD statement","volume":"30","author":"Park","year":"2019","journal-title":"Eur. Radiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s40134-021-00382-6","article-title":"Prostate Cancer Ultrasound: Is Still a Valid Tool?","volume":"9","author":"Carpagnano","year":"2021","journal-title":"Curr. Radiol. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.ijrobp.2018.05.053","article-title":"Repeatability and reproducibility of radiomic features: A systematic review","volume":"102","author":"Traverso","year":"2018","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/5\/780\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T05:34:05Z","timestamp":1772688845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/5\/780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cancers18050780"],"URL":"https:\/\/doi.org\/10.3390\/cancers18050780","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,28]]}}}